As a degenerative joint disease, osteoarthritis (OA) constitutes a major cause of disability that seriously affects the quality of life of a large population of people worldwide. However, effective treatment that can successfully reverse OA progression is lacking until now. The present study aimed to determine whether two small non-coding RNAs miR-29a and miR-140, which are significantly down-regulated in OA, can be applied together as potential therapeutic targets for OA treatment. MiRNA synergy score was used to screen the miRNA pairs that potentially synergistically regulate OA. An in vitro model of OA was established by treating murine chondrocytes with IL-1β. Transfection of miR-29a and miR-140 via plasmids was investigated on chondrocyte proliferation and expression of nine genes such as ADAMTS4, ADAMTS5, ACAN, COL2A1, COL10A1, MMP1, MMP3, MMP13 and TIMP metal-lopeptidase inhibitor 1 (TIMP1). Western blotting was used to determine the protein expression level of MMP13 and TIMP1, and ELISA was used to detect the content of type II collagen. Combined use of miR-29a and miR-140 successfully reversed the destructive effect of IL-1β on chondrocyte proliferation, and notably affected the MMP13 and TIMP1 gene expression that regulates extracellular matrix. Although co-transfection of miR-29a and miR-140 did not show a synergistic effect on MMP13 protein expression and type II collagen release, but both of them can significantly suppress the protein abundance of MMP13 and restore the type II collagen release in IL-1β treated chondrocytes. Compared with single miRNA transfection, cotransfection of both miRNAs exceedingly abrogated the suppressed the protein production of TIMP1 caused by IL-1β, thereby suggesting potent synergistic action. These results provided novel insights into the important function of miRNAs’ collaboration in OA pathological development. The reduced MMP13, and enhanced TIMP1 protein production and type II collagen release also implies that miR-29a and miR-140 combination treatment may be a possible treatment for OA.

Taiyuan City in the eastern Loess Plateau has experienced severe ecological problems caused by urban expansion. For cities undergoing rapid urbanization, building an ecological security pattern (ESP) is an effective means to improve urban resilience. Here, geographic information systems (GIS) were used to analyze, manipulate, and visualize urban ecological multi-source information and remote sensing (RS) for the history of land use/land-cover (LULC) changes and the structure of the urban ecological system. Four important ecosystem service functions were estimated: soil conservation, habitat quality, water yield, and carbon storage. The minimum cumulative resistance (MCR) model was combined with the circuit theory method to determine the ecological corridors, pinch points, and barrier points. Our results showed that: (1) from 1980 to 2020, Taiyuan’s built-up area showed increased construction land and enhanced landscape fragmentation. The decline in cultivated land was mainly attributed to construction land. During the period from 2000 to 2010, a greater amount of land was changed in Taiyuan than in other periods; (2) The ecosystem service evaluation based on the LULC in 2020 revealed that the central urban area was lower than the other areas; (3) 38 ecological source sites were identified, accounting for 16% of the total study area. An area of 106 km2 was allocated to construct 79 ecological corridors. We identified 31 ecological pinch points and 6 ecological barrier points; (4) an ESP optimization governance model of “two rings, four zones, and nine corridors” was proposed. Our study provides theoretical guidance for sustainable development and ecological design in Taiyuan City and other regions.

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